Rubinstein-Taybi syndrome is a genetic syndrome characterized by facial abnormalities, broad thumbs, broad toes, mental retardation and other abnormalities. It is due to mutations in the gene encoding CREB Binding Protein (CBP), although the link between the mutations and the clinical phenotype is not understood. CBP is a protein that is thought to play a critical role in thyroid hormone action--it is a co-activator protein that forms a bridge between the thyroid hormone receptor and the transcription machinery, thus transmitting the signal from thyroid hormone (T3) to allow regulation of gene expression. The CBP mutations that encompass Rubinstein-Taybi syndrome are diverse, and hence there is genetic heterogeneity in this condition. The hypothesis to be tested is that at least some of these CBP mutations disrupt the ability of CBP to function as a T3 receptor co-activator, resulting in a state of thyroid hormone resistance.